Survival of patients with metastatic HER2 positive gastro-oesophageal cancer treated with second-line chemotherapy plus trastuzumab or ramucirumab after progression on front-line chemotherapy plus trastuzumab

BACKGROUND: The role of continuing anti-HER2 therapy beyond progression on front-line therapy in patients with metastatic HER2 positive gastro-oesophageal cancer (GEC) is unclear. Continued chemotherapy plus trastuzumab (CT) has never been compared with the current standard second-line treatment, chemotherapy plus ramucirumab (CR). METHODS: The Flatiron Health electronic health record derived database, a nationwide database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, was reviewed for patients with metastatic HER2 positive GEC who received first-line CT, followed by second-line CT or CR. Survival from second-line therapy (SST) and time to next therapy or death (TTNTD) were compared using Kaplan-Meier curves and logrank analysis. RESULTS: 133 patients with metastatic HER2 positive GEC who received first-line CT were identified. 32 received second-line CR and 101 received CT. Median SST for patients treated with CT versus CR was 10.2 months (IQR 5.1–20.8) and 6.8 months (IQR 2.4–20.2), respectively (p=0.29). Median TTNTD for second-line CT versus CR was 4.9 months (IQR 2.8–9.8) and 5.1 months (IQR 2.3–7.5), respectively (p=0.65). Patients who received second-line CT were more likely to receive a multiagent chemotherapy backbone (76% vs 3%, p≤0.001). CONCLUSIONS: This analysis showed no significant difference in SST for patients treated with second-line CT versus CR. Further studies are needed to clarify the role of trastuzumab in the second line, especially in patients with confirmed retention of HER2 positivity following progression.